Lignin-based microparticles for the controlled release of agricultural actives

ABSTRACT

A method of producing lignin-based matrix microparticles for the controlled release of an agricultural active includes forming an emulsion of an organic solution in an aqueous solution, wherein the organic solution contains a lignin derivative and an agricultural active in a volatile organic solvent and the aqueous solution contains an emulsifier; and removing the organic solvent, thereby producing microparticles having a matrix comprising the lignin derivative within which the agricultural active is distributed. Small, spherical lignin-based matrix microparticles that release an agricultural active at a controlled rate are described, as are plants and plant propagation materials that are treated with such microparticles.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of and claims the benefit ofU.S. patent application Ser. No. 10/191,703, filed Jul. 9, 2002 now U.S.Pat. No.7,771,749, which was a non-provisional of U.S. ProvisionalPatent Application No. 60/304,554, filed Jul. 11, 2001, each of which isincorporated by reference herein in its entirety.

BACKGROUND OF THE INVENTION

(1) Field of the Invention

The present invention relates to matrix microparticles for thecontrolled release of agricultural actives, and more particularly tomethods of producing lignin-based matrix microparticles for thecontrolled release of agricultural actives.

(2) Description of the Related Art

Pesticides, herbicides, plant growth regulating compounds and otherrelated compounds are widely used to protect plants from diseases andpests and ultimately to increase crop yield or value. In addition to thepotential benefits that such compounds promise, however, many of thesematerials are toxic to humans and other animals. Some can be harmful tothe plants they are intended to protect. Thus, the consequences ofunanticipated contact with such compounds over a long term or at highconcentrations is undesirable. Moreover, because such compounds arecomplex molecules, most of which must be chemically synthesized, theyare often expensive to produce, and can be chemically fragile.Therefore, in addition to the potential environmental harm that can becaused by leaching, blowing and other movement of the materials awayfrom the area of initial application, some of these compounds arequickly degraded by ultraviolet (UV) light. These losses reduce theeffectiveness of the compound and increase the amount that must beapplied in order to provide a desired benefit.

One strategy for managing the safety and effectiveness of many of thesebiologically active compounds has been to provide them as controlledrelease formulations. Such formulations provide the active within astructure which limits the rate of transfer of the active into thesurrounding environment and minimizes the movement of the active awayfrom the site of application. General information on controlled releaseformulations for agricultural actives can be found in:Controlled-Release Delivery Systems for Pesticides, H. B. Scher, Ed.,Marcel Dekker, Inc., NY (1999), Microencapsulation, Benita, S., (Ed.),Marcel Dekker, Inc., New York (1996), Controlled Delivery ofCrop-Protection Agents, Wilkins, R. M., (Ed.), Taylor & Francis Ltd.,London (1990), and Fernandez-Perez, M. et al., J. Agric. Food Chem.,46:3828 (1998), among others.

Common forms of controlled release formulations include microcapsules,microparticles and granules. Generally, microcapsules are considered tobe particles of 1-100 microns in size that are composed of a distinctwall and a core that contains the active. Microparticles is a term thatis generally used to describe matrix particles of 1-100 microns in sizethat have the active more or less uniformly distributed or dispersedwithin the matrix. Granules are matrix particles that are 0.2-2 mm insize with the active more or less uniformly distributed or dispersedthroughout the matrix.

Each of these controlled release forms has advantages and disadvantages.For example, microcapsules that are formed by coating small solidparticles of an active with a barrier material, often a polymer, areoften of uneven shape and have uneven coating thickness over the surfaceof the particle—some even having exposed surfaces of the active.Accordingly, it is often difficult to assure predictable and evenrelease of the active from such coated particles. Some coated particlespermit high levels of the active at the surface and this can increasethe exposure of handlers to the active and can result in rapid loss ofthe active upon application. These same disadvantages are also presentin granules that have been produced by absorption of the active onto acarrier material.

Microcapsules having regular spherical shape and uniform walls can beformed by in situ polymerization of a polymeric barrier wall at thesurface of droplets in emulsions. A common example is the reaction of apolyamine in one liquid phase with a polyisocyanate in another phase toform a polyurea wall surrounding a core containing an active. See, e.g.,U.S. Pat. No. 5,525,595 to Seitz et al. However, the reactants that aresuitable for such formulations are somewhat limited, and this can limitthe types of active with which this technique can be successfully used.Furthermore, the production of such microcapsules having consistentproperties requires careful control and expensive reactants.

Uniformly spherical particles, which demonstrate predictable and regularrelease rates, can also be provided by the formation of matrixmicroparticles. General information on the production of matrixmicroparticles can be found in Controlled release of pesticides frommicroparticles, Park, D. J., et al., Ch. 4, pp. 89-137, and inDispersible microparticles, Smith, K. L., Ch. 5, pp. 137-149, both inControlled-Release Delivery Systems for Pesticides, Scher, H. B., Ed.,Marcel Dekker, Inc., New York (1999).

It is generally known that the release of a molecule, such as anagricultural active, from a matrix microparticle depends upon, amongother things, the size and geometry of the particle and thecompatibility between the active and the matrix material. Moreover, thecompatibility between the active and the matrix material can also affectwhether it is possible to successfully produce a useful matrixmicroparticle from a given active and a given matrix material. Forexample, if there is insufficient compatibility between the active andthe matrix material, a majority of the active can be excluded from thematrix microparticle during the formation process. Such a product ischaracterized by a high concentration of the active present as crystals,or on the surface of the microparticles, and results in uncontrolledrelease of the active into the environment. A microparticle formulationhaving high levels of the active outside the particles, or on thesurface of the particles, is usually found to have a high readilyextractable active (REA) value.

Because of the often complex chemistries of modern agricultural actives,it has not been possible to predict a priori which combinations ofactive and matrix material can be expected to yield effective matrixmicroparticles having low REA values. For example, recently introducedchloronicotinyls have been shown to be useful as insecticides (See.,e.g., U.S. Pat. Nos. 5,994,331, 6,077,860, 6,114,362), but theirsuccessful inclusion in controlled release forms that are capable ofsustained release over periods longer than a few days has beendifficult. See, e.g., Gonzalez-Pradas, E., Pestic. Sci., 55:546-552(1999), and Fernandez-Perez, M., J. Agric. Food Chem., 46(9):3828-3834(1998).

Because controlled release formulations that are designed foragricultural uses necessarily must be of a lower cost than, for example,medical applications, it is important to provide such formulations thatcan be produced economically and efficiently. Moreover, because suchformulations are usually applied directly to plants or into the soil, itis important that the particles be biodegradable, so as not to persistin the environment.

Due to its wide availability and properties as a UV protectant, ligninhas been used as a carrier or adjuvant for actives in agriculturalcompositions. For example, Dilling et al., in U.S. Pat. Nos. 4,751,247and 4,797,157, describe the use of amine salts of ligonulfonates as asequestrant in pesticide compositions. The use of alkali lignin as apesticide dispersant was taught in U.S. Pat. Nos. 3,726,850 and3,992,532. U.S. Pat. No. 3,813,236 described the covalent bonding of apesticide to a lignin substrate, and U.S. Pat. No. 3,929,453, reissuedas Re. No. 29,238, taught a slow release composite produced byco-precipitation of an alkali lignin or the removal of a common solventfrom a lignin-pesticide mixture.

Other lignin-based sustained release formulations were described in U.S.Pat. Nos. 4,184,866, 4,244,728 and 4,244,729, each of which teaches thecross-linking of lignin with epichlorohydrin or formaldehyde.

In U.S. Pat. No. 4,381,194, the adsorption of a herbicide or fungicideonto particles of a water-insoluble alkali lignin and a surfactant,where the lignin had a mean particle size of from 0.5 to 5 microns indiameter. In U.S. Pat. Nos. 4,624,694 and 4,752,319, DelliCollidescribed the use of a similar lignin slurry, except without theherbicide or fungicide, as a method of crop seed treatment to provide anincrease in emergence of seedlings.

Lignosulfonates, in combination with a protein such as a high bloomgelatin, were reported in U.S. Pat. No. 5,552,149 to be useful for theformation of microcapsules that were resistant to UV degradation.

Other lignin derivatives, such as for example, lignin acetate, have beenreported to be useful for applications such as acting as a binder inwater-based printing ink compositions. (See, e.g., U.S. Pat. No.4,612,051).

Accordingly, therefore, it would be useful to provide controlled releasemicroparticles and formulations for agricultural actives that could beproduced from readily available, biodegradable materials that would havea low environmental impact. It would also be useful if suchmicroparticles would stabilize the active against UV degradation.Furthermore, it would be useful if such microparticles could be made tobe sufficiently small so that they could be used effectively ascomponents in a seed coating, but still capable of maintaining therelease of the active over a period of time of several weeks, or months.

SUMMARY OF THE INVENTION

Briefly, therefore the present invention is directed to a novel methodof producing lignin-based matrix microparticles for the controlledrelease of an agricultural active, the method comprising the steps of:

forming an emulsion of an organic solution in an aqueous solution,wherein the organic solution contains a lignin derivative and anagricultural active in a volatile organic solvent and the aqueoussolution contains an emulsifier; and

removing the organic solvent, thereby producing microparticles having amatrix comprising the lignin derivative within which the agriculturalactive is distributed.

The present invention is also directed to a novel formulation for thecontrolled release of an agricultural active, the formulation comprisingpredominantly spherical matrix microparticles having a matrix of alignin derivative within which an agricultural active is distributed.

The present invention is also directed to a novel method of treating aplant or its propagation material, the method comprising contacting theplant or its propagation material with the formulation described justabove.

The present invention is also directed to a novel treated plant or itspropagation material comprising a plant or its propagation material thathas been contacted with the formulation described above.

Among the several advantages found to be achieved by the presentinvention, therefore, may be noted the provision of controlled releasemicroparticles for agricultural actives that can be produced fromreadily available, biodegradable materials that have a low environmentalimpact, and the provision of such materials and formulations that canstabilize the active against UV degradation, and the provision of suchmicroparticles that are sufficiently small so that they can be usedeffectively as components in a seed coating, but still are capable ofmaintaining the release of the active over a period of time of severalweeks, or months.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows electron micrographs of lignin-based matrix microparticlesof the present invention which contain imidacloprid taken atmagnifications of 100× (1(a)), 500× (1(b)), 1000× (1(c)), and 2000×(1(d));

FIG. 2 shows a release rate curve for the release of imidacloprid fromlignin-based matrix microparticles of the present invention into anexcess of water at room temperature, and indicates a half-life ofapproximately 1000 hours;

FIG. 3 shows electron micrographs of the microparticles shown in FIG. 1after submersion in water for 42 days (about 1,000 hours) taken atmagnifications of (a) 100×, (b) 500×, (c) 1000×, and (d) 2000×, whereinit is apparent that the microparticles were physically breaking downinto cracked spheres or smaller fragments;

FIG. 4 shows a release rate curve for the release of imidacloprid fromlignin-based matrix microparticles having a higher loading ofimidacloprid than the microparticles of FIG. 2, where the release wasmeasured into an excess of water at room temperature, and indicates ahalf-life of approximately 2000 hours;

FIG. 5 shows a release rate curve for the release of imidacloprid fromlignin-based matrix microparticles having a smaller size than themicroparticles of FIG. 2, where the release was measured into an excessof water at room temperature, and indicates a half-life of approximately2000 hours; and

FIG. 6 shows a release rate curve for the release of silthiopham fromlignin-based matrix microparticles of the present invention into anexcess of water at room temperature.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In accordance with the present invention, it has been discovered thatlignin-based matrix microparticles for the controlled release of anagricultural active can be prepared by forming an aqueous solution thatincludes an emulsion stabilizer, forming an organic solution bydissolving a lignin derivative and an agricultural active in a volatileorganic solvent, and combining the aqueous solution and the organicsolution in a manner that results in the formation of an emulsion of theorganic solution in the aqueous solution. The organic solvent can thenbe removed from the emulsion, with the resulting production ofmicroparticles having a matrix comprising the lignin derivative withinwhich the agricultural active is distributed.

The subject lignin-based matrix microparticles are easy to produce withconventional equipment and techniques and can be designed to providelong-term release of the agricultural active that is enclosed within thematrix. Release half-lives of over about 2000 hours have been reported,even for microparticles of less than about 20 microns in average size.This unexpectedly advantageous combination of properties permits thesubject microparticles to be used efficiently in seed treatments thatrequire protection of long duration, such as, for example, the treatmentof winter wheat seed, which benefits from significant residual activityat even three or four months after planting.

The term “matrix”, as used herein, means a continuous solid phase of oneor more lignin-based binder compounds throughout which is distributed asa discontinuous phase one or more of the subject agricultural actives.Optionally, a filler and/or other components can also be present in thematrix.

The subject method of production captures the active within themicroparticle with a high level of efficiency, but avoids high levels ofeasily lost, or readily extractable active (REA).

The lignin-based microparticles of the present invention can be producedby providing an organic solution that contains a lignin derivative andan agricultural active in a volatile organic solvent. The organicsolution is intermixed with an aqueous solution to form an emulsion. Ithas been found to be easier to form a stable emulsion having thepreferred droplet, or particle, size, when a suitable emulsifier ispresent when the two solutions are intermixed. It is preferred that theemulsion be an oil-in-water type emulsion in which the organic solutionforms the discontinuous phase and the aqueous solution forms thecontinuous phase. After the emulsion has been formed, the organicsolvent is removed, thereby producing microparticles having a matrixcomprising the lignin derivative within which the agricultural active isdistributed.

The preferred emulsifier is one that is compatible with the agriculturalactive and one in whose presence an oil-in-water emulsion is more stablethat an emulsion in which the emulsifier is absent. When it is said thatthe preferred emulsifier is compatible with the agricultural active, itis meant that the emulsifier is dispersible in, or preferably, solublein the active.

Useful emulsifiers include anionic, cationic, nonionic and amphotericemulsifiers.

Examples of useful anionic emulsifiers include soap-alkali metal saltsof fatty acids, such as sodium stearate; salts of tall oil acids; alkylnaphthalene sulfonates and condensates, such as Lomar D (Henkel); fattyalcohol monoesters of sulfonic acids, such as Conco Sulfate M; linearalkyl benzene sulfonates, such as sodium n-dodecylbenzenesulfonate;lignin sulfonates; alkane and α-olefin sulfonates, such as Bio-TergeAS-40 (Stepan); sulfosuccinates, such as Anionyx 12s (Stepan); phosphateesters, such as Bio-SURF pbc-430 (Lonza); sulfated ethoxylates of fattyalcohols, such as Avirol SA-4110 (Henkel); and N-acyl-N-alkyl taurates,such as Igepon T (GAF).

Examples of useful cationic emulsifiers include quaternary ammoniumsalts, such as Algepon AK (Sandoz); and alkylated pyridinium salts, suchas Damox 1010 (Ethyl).

Examples of useful nonionic emulsifiers include alkanolamides, such asComperlan KD (Henkel); ethoxylated fatty alcohols, such as Brij (ICI);alkyl phenol polyethoxylates, such as Triton X-100 (Rohm and Haas);fatty acid esters; glycerol esters and glycol esters, such as Cutine GMS(Henkel); esters of propylene glycol, sorbitan and ethoxylated sorbitan,such as Tween 60 (ICI) and Span 20 (ICI).

Examples of useful amphoteric emulsifiers include betaines, such asAmphosol (Stepan); and alkyl amine oxides, such as Admox 1214 (Ethyl).

Other useful emulsifiers include polymeric surfactants, such ascellulose deriviatives; silicone surfactants (dimethylsiloxane polymerswith hydrophile); and perfluorocartoxylic acid salts andfluorosurfactants.

Other useful emulsifiers are identified by Piirma, I., in PolymericSurfactants, Marcel Dekker, New York (1992), and in U.S. Pat. Nos.4,960,814, 4,911,736 and 4,846,986.

Cellulose derivatives have been found to be preferred emulsifiers, andmethylcellulose is a more preferred emulsifier.

The emulsifier can be added to the mixture of the organic solution andthe aqueous solution in any manner. For example, it can be added neat toeither the aqueous solution or to the organic solution, or to a mixtureof the two solutions. A preferred method of adding the emulsifier is tointermix the emulsifier with water to form an aqueous solution prior tomixing the aqueous solution with the organic solution. Whenmethylcellulose is used as the emulsifier, it is preferred that it isintermixed into cold water in any manner that will result in theformation of an aqueous solution of the methylcellulose.

When the emulsifier is intermixed with the aqueous solution, it can beused in any amount that will result in the formation of a desiredemulsion between the organic and aqueous solutions. It is preferred thatthe amount of the emulsifier in the aqueous solution be from about 0.1%to about 20% by weight, more preferred from about 0.2% to about 10% byweight, and even more preferred from about 0.5% to about 3% by weight ofthe aqueous solution.

The amount of emulsifier that is useful in the novel method can also beexpressed on the basis of the amount of the lignin derivative. On thisbasis, any amount of the emulsifier can be used that will result in theformation of a desired emulsion between the organic and aqueoussolutions. It is preferred that an amount of the emulsifier be used thatprovides a weight ratio between the emulsifier and the ligninderivative, on a dry basis, of from about 1:1 to about 1:100, morepreferred is an emulsifier-to-lignin derivative weight ratio of fromabout 1:2 to about 1:50, even more preferred is a ratio of about 1:5 toabout 1:20, and yet more preferred is a ratio of about 1:10 to about1:15.

The organic solvent that is useful in the method of the presentinvention can be any solvent that has a normal boiling point that islower than the normal boiling point of water and has a low solubility inwater. It is preferred that the organic solvent is one that has a normalboiling point of from about 0° C. to about 100° C. and a solubility inwater of less than about 20 g/100 ml at 20° C., more preferred that theorganic solvent is one that has a normal boiling point of from about 20°C. to about 90° C. and a solubility in water of less than about 10 g/100ml at 20° C., and even more preferred that the organic solvent is onethat has a normal boiling point of from about 30° C. to about 80° C. anda solubility in water of less than about 5 g/100 ml at 20° C.

Organic solvents that are useful in the present method include methylenechloride, chloroform, ethylacetate, cyclopentane, pentane,2-methylbutane, methyl cyclopentane, hexane, cyclohexane, heptane,2-methylpentane, 3-methylpentane, 2-methylhexane, 3-methylhexane,2,3-dimethylbutane, methylcyclohexane, 2,3-dimethylpentane,2,4-dimethylpentane, benzene, 1-pentene, 2-pentene, 1-hexene, 1-heptene,cyclohexene, 1-butanol, ethyl vinyl ether, propyl ether, isopropylether, butyl vinyl ether, butyl ethyl ether, 1,2-epoxybutane, furan,tetrahydropyran, 1-butanal, 2-methylpropanal, 2-pentanone, 3-pentanone,cyclohexanone, fluorobenzene, hexafluorobenzene, ethyl formate, propylformate, isopropyl formate, vinyl acetate, isopropyl acetate, ethylpropionate, methyl acrylate, ethyl acrylate, methyl methacrylate,chloroethane, 1-chloropropane, 2-chloropropane, 1-chlorobutane,2-chlorobutane, 1-chloro-2-methylpropane, 2-chloro-2-methylpropane,1-chloro-3-methylbutane, 3-chloropropene, tetrachloromethane,1,1-dichloroethane, 1,2-dichloroethane, 1,2-dichloropropane,1,1,1-trichloroethane, 1,1-dichloroethylene, 1,2-dichloroethylene,trichloroethylene, bromoethane, 1-bromopropane, 2-bromopropane,1-bromobutane, 2-bromobutane, 2-bromo-2-methylpropane, bromoethylene,iodomethane, iodoethane, 2-iodopropane, trichlorofluoromethane,dichlorofluoromethane, dibromofluoromethane, bromochloromethane,bromochlorofluoromethane, 1,1,2-trichloro-1,2,2-trifluoroethane,1,1,2,2-tetrachlorodifluoroethane, 1,2-dibromotetrafluoroethane,1,2-dibromo,-1,1-difloroethane, 1,1-dichloro-2,2-difluoroethylene,propionitrile, acrylonitrile, methacrylonitrile, triethylamine, carbondisulfide, 1-butanethiol, methyl sulfide, ethyl sulfide, andtetramethylsilane. Any of these solvents can be used alone or in amixture with any one or more of the other solvents.

Methylene chloride, chloroform and ethylacetate are preferred solvents,and methylene chloride has been found to be a more preferred solvent.

Lignin derivatives that are useful for forming a matrix for the matrixmicroparticles of the present invention include those that are solublein the organic solvent in an amount of at least about 1% by weight at20° C. When the terms “lignin derivative” are used herein, such termsare meant to include native lignins and any materials that are derivedfrom native lignin, which meet the organic solubility criteria that isrequired for the material. It is preferred that the lignin derivative isone that is soluble in the organic solvent in an amount of at leastabout 10% by weight at 20° C. A preferred lignin derivative compriseslignin acetate.

The present matrix microparticles contain an agricultural active. Whenthe terms “agricultural active” are used herein, they are meant toinclude any compound that directly or indirectly has a beneficial effecton a plant or its propagation material. For example, the termsagricultural active are meant to include herbicides, pesticides,fertilizers, growth factors, and the like.

The preferred agricultural active of the present invention is one thatis soluble in water at 20° C. in an amount of less than about 2% byweight and is soluble in the organic solvent in an amount of at leastabout 1% by weight, and more preferred is an active that is soluble inwater at 20° C. in an amount of less than about 2% by weight and issoluble in the organic solvent in an amount of at least about 5% byweight.

The preferred agricultural active is one that also is sufficientlycompatible with the lignin derivative that no crystals of the activeform during the production of the subject microparticles when the activeis present in an amount of at least about 5% by weight of the ligninderivative. It is more preferred that the active is sufficientlycompatible with the lignin derivative that no crystals of the activeform during the production of the subject microparticles when the activeis present in an amount of at least about 10% by weight, even morepreferred is an active where no crystals form when the active is presentin an amount of at least about 20% by weight of the lignin derivative.

Useful agricultural actives in the present invention include materialsselected from the group consisting of pesticides, herbicides and growthregulators. Examples of useful actives include acylalanines,alkanamides, amidines, anilides, anilinopyrimidines, aromatichydrocarbons, chlorophenyls, arylaminopropionic acids, aryloxyalkanoicacids, aryloxyalkanoic acids, aryloxyphenoxypropionates, auxins,avermectins, benzamides, benzenecarboxilic acids, benzilates,benzimidazoles, benzofurans, benzoic acids, benzonitriles,benzothiadiazinones, benzothiazolones, benzotriazines, benzoylureas,bipyridyliums, bis-carbamates, butyrolactones, carbamates,carbamoyltriazoles, chloroacetamides, chloronitriles, chloronicotinyls,cinnamic acids, coumarin anticoagulants, cyclodiene organochlorines,cyclohexanedione oximes, cytokinins, diacylhydrazines, dicarboximides,2-dimethylaminopropane-1,3-dithiols, dimethyldithiocarbamates,dinitroanilines, dinitrophenols, diphenyl ethers, dithiocarbamates,DMI:imidazoles, DMI:pyridines, DMI:pyrimidines, DMI:triazoles,gibberellins, glycine derivatives, guanidines, halogenated alkanoicacids, hydroxyanilides, hydroxylbenzonitriles, imidazoles,imidazolinones, indandione anticoagulants, isoxazoles, isoxazolidinones,juvenile hormone mimics, MBI:dehydrases, morpholines,multi-site:alkylenebis(dithiocarbamates), multi-site: chloronitriles,multi-site: dimethyldithiocarbamates, multi-site: guanidines,multi-site: inorganics, multi-site: phenylphridinamines, multi-site:phosphonates, multi-site: phthalimides, multi-site: quinones,multi-site: sulphamides, natural pyrethrins, neonicotinoids,nitromethylene: neocorticoids, non-ester pyrethroids, N-phenylcarbamates, N-phenylphthalimides, organoarsenics, organochlorines,organophosphorous compounds, organotins, oxadiazines, oxadiazoles,oxathlins, oxozolidinediones, oxazolidinones, oxime carbamates,oxyacetamides, phanylamide: acylalanines, phenylamide: butyrolactones,phenylamide: oxazolidinones, phenylpyrazole herbicides, phenypyrazoleinsecticides, phenylpyridazines, phenylpyridinamines, phenylpyrroles,phenylureas, pheromones, phosphinic acids, phosphonates,phosphoroamidates, phosphorodithioates, phosphorothiolates,phthalamates, phthalimides, piperazines, polyoxins, pyrazoles,pyrazoliums, pyrethrins, pyrethroids, pyrethroid non-esters,pyridazinones, pyridazinones, pyridazinone analogues, pyridines,pyridinecarboxamides, pyridinecarboxylic acids, pyrimidindiones,pyrimidines, pyrimidinols, pyrimidinyl carbinols, pyrimidinyloxybenzoiccompounds, pyrimidinyloxybenzoic analogues, quaternary ammoniumcompounds, quinolines, quinolinecarboxylic acids, quinones,semi-carbazones, strobilurin type compounds,sulfonylaminocarbonyltriazolinones, sulfonylureas, sulfamides, syntheticauxins, tetrazines, tetrazolinones, thiadiazoles, thiocarbamates,1,3,5-triazines, 1,2,4-triazinones, triazoles, triazolinones,triazolpyrimidines, triketones, uracils and ureas.

Examples of useful strobilurin type compounds include metominostrobin,picoxystrobin, famoxadone, azoxystrobin, kresoxim-methyl andtrifloxystrobin.

Examples of useful neonicotinoids include acetamiprid, imidacloprid andthiamethoxam.

Examples of useful herbicides include phenoxy acetic acids, such as2,4-D and MCPA; phenoxy propionic acids, such as dichlorprop (2,4-DP)and mecoprop (MCPP); phenoxy butyric acids, such as 2,4-DB and MCPB;benzoic acids, such as dicamba (Banvel, Clarity, Vanquish); picolinicacid and related compounds, such as picloram (Tordon), triclopyr(Garlon, Grandstand, Remedy, Turflon); clopyralid (Lontrel, Reclaim,Stinger, Transline), and quinclorac (Facet); naptalam (Alanap);semicarbones, such as diflufenzopyr-sodium (BAS 654, Distinct);chloro-s-triazines, such as atrazine (Aatrex, Atrazine), simazine(Princep), and cyanazine (Bladex); methoxy-s-triazines, such as prometon(Pramitol); methylthio-s-triazines, such as ametryn (Evik), andprometryn (Caparol, Cotton-Pro, Gesagard); other triazines, such ashexazinone (Velpar), and metribuzin (Sencor, Lexone); substituted ureas,such as diuron (Karmex), fluometuron (Cotoran), linuron (Lorox), andtebuthiuron (Spike); uracils, such as bromacil (Hyvar), and terbacil(Sinbar); benzothiadiazoles, such as bentazon (Basagran); benzonitriles,such as bromoxymil (Buctril); phenylcarbamates, such as desmedipham(Betanex), and phenmedipham (Spin-aid); pyridazinones, such as pyrazon(Pyramin); phenypyriddazines, such as pyridate (Tough, Lentagran);propanil (Stam, Stampede); amitrole (Amitrol T); clomazone (Command);fluridone (Sonar); pyridazinones, such as norflurazon (Zorial, Evital,Solicam, Predict); isoxazoles, such as isoxaflutole (Balance);dinitroanilines, such as benefin (Balan), ethalfluralin (Sonalan,Curbit), oryzalin (Surflan), pendimethalin (Prowl, Pendulum, Pentagon),prodiamine (Barricade, Endurance, Factor), and trifluralin (TreflanTrifluralin); pyridines, such as dthiopyr (Dimension), and thiazopyr(Visor); amides, such as pronamide (Kerb); DCPA (Dacthal);carbamothioates (thiocarbamates), such as EPTC (Eptam, Eradicane,Eradicane Extra), cycloate (Ro-Neet), pebulate (Tillam), and triallate(Far-Go, Avandex BW), butylate (Sutan +), molinate (Ordram), thiobencarb(Bolero, Abolish), and vernolate (Vernam); seedling root inhibitingamides, such as napropamide (Devrinol); seedling root inhibitingphenylureas, such as siduron (Tupersan); bensulfide (Prefar, Betasan,Bensumec); chloroacetamides, such as acetochlor (Harness, Surpass,Topnotch); dimetenamid (Frontier), propachlor (Ramrod); alachlor (Lasso,Micro-Tech, Partner), and metolachlor (Dual, Pennant); glyphosate(Roundup, Rodeo); sulfosate (Touchdown); sulfonylureas, such asbensulfuron (Londax), chlorsulfuron (Glean, Telar), halosulfuron(Permit, Battalion, Manage), nicosulfuron (Accent), prosulfuron (Peak),rimsulfuron (Matrix, Elim, Titus, Prism), thifensulforon (Pinnacle),tribenuron (Express), chlorimuron (Classic), ethametsulfuron (Muster),metsulfuron (Ally, Escort), primisulfuron (Beacon), oxasulfuron(Expert), triasulfuron (Amber), and triflusulfuron (Upbeet);imidazolinones, such as imazamethabenz (Assert), imazamox (Raptor),imazapic (Cadre, Contend), imazapyr (Arsenal, Chopper, Stalker),imazaquin (Scepter, Image) and imazethapyr (Pursuit);aryoxyphenoxyproprionates, such as diclofop-methyl (Hoelon, Hoe-Grass,Illoxan), fenoxaprop-ethyl (Acclaim, Horizon, Excel), fenoxaprop-p-ethyl(Option II, Puma, Whip 360, Horizon), fluazifop-p-butyl (Flusilade2000), haloxyfop (Verdict, Gallant), and quizalofop-p-ethyl (Assure II);cyclohexanediones, such as clethodim (Envoy, Prism, Select), sethoxydim(Poast, Poast Plus, Prestige, Torpedo, Ultims, Vantage), and tralkoxydim(Achieve); nitriles, such as dichlobenil (Casoron, Dyclomec);benzamides, such as isoxaben (Gallery); quinclorac (Facet); dilutesulfuric acid; monocarbamide dihydrogen sulfate (Enquick); herbicidaloils; bipyridyliums, such as diquat (Diquat, Reward), and paraquat(Gramoxanone Extra, Cyclone, Starfire); diphenylethers, such asacifluorofen (Blazer, Status), fomesafen (Flexstar, Reflex), lactofen(Cobra), and oxyfluorfen (Goal); oxidiazoles, such as fluthiacet(Action), and oxadiazon (Ronstar); n-phenylheterocycles, such ascarfentrazone (Affinity, Aim), flumiclorac (Resource), and sulfentrazone(Authority, Cover, Spartan); glufosinate (Finale, Liberty, Rely);organic arsenicals, such as DSMA, and MSMA; asulam (Asulox); endothall(Accelerate, Aquathol, Des-I-Cate); ethofumesate (Nortron, Prograss);fosamine (Krenite); difenzoquat (Avenge); and TCA (Nata).

Examples of useful fungicides and fungicidal mixtures includefludioxonil, fluquinconazole, silthiopham, difenoconazole, a mixture offludioxonil and fluquinconazole or4,5-dimethyl-N-2-propenyl-2-(trimethylsilyl)-3-thiophencarboxamid; amixture of difenoconazole and fluquinconazole or4,5-dimethyl-N-2-propenyl-2-(trimethylsilyl)-3-thiophencarboxamid; and amixture as taught in WO 00/27200 of a thienol[2,3-d]pyrimidin-4-one andan azole fungicide, an anilinopyrimidine fungicide, a morpholinefungicide, a strubilurin compound, a pyrrole compound, a phenylamide, ora dithiocarbamate fungicide.

Preferred agricultural actives include imidacloprid, acetamiprid,thiamethoxam, TI-435 (clothiamidin), simeconazole, fluquinconazole,tebuconazole, silthiopham, terbufos, chlorpyrifos, fipronil,chlorethoxyfos, tefluthrin, fipronif, carbofuran, tebupirimfos,methoprene, hydroprene, and mixtures thereof. Imidacloprid has beenfound to be particularly preferred as the agricultural active of thepresent invention.

When imidacloprid is an agricultural active in the subject matrixmicrocapsules, it has been found to be preferred that the organicsolvent comprises methylene chloride and the lignin derivative compriseslignin acetate.

When the aqueous solution and the organic solution are intermixed, theycan be mixed by any method that is known in the art to provide anemulsion. It is preferred that the step of forming an emulsion includesmixing the aqueous solution and the organic solution under conditions ofhigh shear and thereby forming an oil-in-water emulsion wherein theorganic solution forms the discontinuous phase and the aqueous solutionforms the continuous phase.

During the time that high shear is being applied to the mixture, it ispreferred that the temperature of the solutions be maintainedsufficiently low that a significant amount of the organic solvent is notlost by evaporation. It is more preferred that the temperature of theaqueous solution and the organic solution is maintained at a level thatis no higher than 20° C. below the normal boiling point of the organicsolvent during the step comprising forming an emulsion, and yet morepreferred that the temperature is maintained at a level that is nohigher than 30° C. below the normal boiling point of the organicsolvent.

When the organic solvent that is used includes methylene chloride, whichhas a normal boiling point of about 40.1° C., and the agriculturalactive includes imidacloprid, and lignin acetate is at least a majorcomponent of the lignin derivative, it is preferred that the temperatureis maintained below about 10° C., and more preferred that thetemperature be maintained at about 4° C. during formation of theemulsion.

When the emulsion is formed from the aqueous solution and the organicsolution, the emulsion comprises discrete, substantially sphericaldroplets of a discontinuous phase dispersed within a continuous phase.As discussed above, it is preferred that the aqueous phase form thecontinuous phase and the organic phase—containing the lignin derivativeand the agricultural active—form the droplets of the discontinuousphase. It is preferred that the organic solution in the discontinuousphase comprises droplets having an average diameter of no larger thanabout 100 microns. Smaller droplets are also preferred.

After the formation of the emulsion, the liquid droplets of the organicphase are transformed into solid spherical matrix microparticles by theremoval of the organic solvent from the emulsion. Although the solventcan be removed from the emulsion by any means known in the art,evaporation is commonly used to remove the solvent.

When the solvent is removed by evaporation, it has been found to bepreferred to carry out the evaporation at a rate that is sufficientlyslow to permit the formation of matrix microparticles having a matrix ofthe lignin derivative throughout which is dispersed the agriculturalactive, the microparticles also having a majority of the active withinthe microparticles, rather than on the surface of the microparticles oras crystals in the aqueous solution. The presence of a significantportion of the active on the surface of the microparticles or ascrystals in the aqueous solution results in the preparation having ahigh “REA” value. After formation of the emulsion, it is preferred toraise the temperature of the emulsion to increase the evaporation of thesolvent, but to limit the temperature to below the normal boiling pointof the solvent.

When the matrix microparticles are formed by the removal of the solvent,it is preferred that the microparticles are predominantly spherical andhave an average diameter of less than about 100 microns, more preferredthat they have an average diameter of less than about 25 microns, evenmore preferred that they have an average diameter of less than about 10microns. The small spherical microparticles of the present invention donot have to be of the same size, but may be of different sizes within asize range. When it is said that the microparticles have an averagediameter, it is a number average diameter that is referred to.

An advantage of microparticles of such small size is that they may beused in seed coating formulations that have a high degree of adhesion tothe seed. It is known that larger particles, for example, larger thanabout 100 microns in average size, are more susceptible to abrasion andloss from the surface of the seed. Furthermore, smaller particles permita more even distribution of the active over the surface of a seed or aplant, and also formulations that contain the microparticles are easierto process through application equipment such as seed coaters, sprayers,and the like.

The regular spherical shape of the microparticles of the presentinvention is also advantageous, because it insures that the release ofthe active from the particle occurs in a steadier and more predictablepace that if the particles were irregular in shape. When it is said thatthe active is distributed throughout the lignin-based matrix, it shouldbe understood that the distribution does not have to be of anyparticular pattern (i.e., not necessarily homogeneous or evenlydistributed) and can be more at the center, or nearer the surface, andthe active distribution in the matrix can be a molecular mix or can beparticles of the active distributed within the solid lignin derivativematrix.

Unlike many of the lignin-based particles of the prior art, the presentmethod of producing the novel matrix microparticles is free of grindingor milling. The present matrix microparticles are generally spherical inshape, and it is preferred that a preparation of the microparticles hasa level of readily extractable active (REA) that is lower than about20%.

An advantageous feature of the present microparticles is the surprisingcombination of their small size and their ability to continue to releaseactive over an unexpectedly long period of time. Small lignin-basedmicroparticles of the prior art are reported to release most activematerial within a few days, whereas the present microparticles are foundto be capable of releasing the agricultural active into an infinite sinkof water at room temperature for at least 1000 hours.

The present matrix microparticles can be used in the same manner as anyother conventional microparticle or microcapsule that is designed forthe controlled release of an agricultural active. The subjectmicroparticles can be used to treat a plant or its propagation materialby contacting the plant or its propagation material with a formulationthat contains the microparticles. By the terms “plant or its propagationmaterial”, it is meant to include any and all parts of a plant in anystage of growth, as well as any root, shoot, seed, flower,inflorescence, tuber, rhizome, and any other material from which theplant can be started or regenerated. When it is said that themicroparticles are “contacted” with the plant or its propagationmaterial, it is meant to include all direct and indirect contact, suchas, for example, application to the plant, seed, or to the soil in whichthe seed or plant has been or is to be planted.

The microparticles can be applied in a dry formulation, or can beapplied as a slurry or emulsion. They can be used neat or can be mixedwith any other materials that can be useful components of seed or planttreatment formulations. Such materials can include stickers, safeners,herbicides, pesticides, growth regulators, colorants, dyes, stabilizers,surfactants, antioxidants, and the like.

A particularly useful application of the present microparticles is forthe treatment of plant seed. It is preferred that the microparticles areapplied to the seed after the seed have been harvested from the parentplant and before they are themselves planted.

As mentioned above, other conventional inactive or inert ingredients canbe incorporated into the formulation. Such inert ingredients include butare not limited to: conventional sticking agents, dispersing agents suchas methylcellulose (Methocel A15LV or Methocel A15C, for example, serveas combined dispersant/sticking agents for use in seed treatments),polyvinyl alcohol (e.g., Elvanol 51-05), lecithin (e.g., Yelkinol P),polymeric dispersants (e.g., polyvinylpyrrolidone/vinyl acetate PVPNAS-630), thickeners (e.g., clay thickeners such as Van Gel B to improveviscosity and reduce settling of particle suspensions), emulsionstabilizers, surfactants, antifreeze compounds (e.g., urea), dyes,colorants, and the like. Further inert ingredients useful in the presentinvention can be found in McCutcheon's, vol. 1, “Emulsifiers andDetergents,” MC Publishing Company, Glen Rock, N.J., U.S.A., 1996.Additional inert ingredients useful in the present invention can befound in McCutcheon's, vol. 2, “Functional Materials,” MC PublishingCompany, Glen Rock, N.J., U.S.A., 1996.

The microparticle formulations of the present invention can be appliedto seeds by any standard seed treatment methodology, including but notlimited to mixing in a container (e.g., a bottle or bag), mechanicalapplication, tumbling, spraying, and immersion. Any conventional activeor inert material can be used for contacting seeds with microparticlesaccording to the present invention, such as conventional film-coatingmaterials including but not limited to water-based film coatingmaterials such as Sepiret (Seppic, Inc., Fairfield, N.J.) and Opacoat(Berwind Pharm. Services, Westpoint, Pa.).

The subject microparticles can be applied to a seed as a component of aseed coating. Seed coating methods and compositions that are known inthe art are useful when they are modified by the addition of themicroparticles of the present invention. Such coating methods andapparatus for their application are disclosed in, for example, U.S. Pat.Nos. 5,918,413, 5,891,246, 5,554,445, 5,389,399, 5,107,787, 5,080,925,4,759,945 and 4,465,017. Seed coating compositions are disclosed, forexample, in U.S. Pat. Nos. 5,939,356, 5,882,713, 5,876,739, 5,849,320,5,834,447, 5,791,084, 5,661,103, 5,622,003, 5,580,544, 5,328,942,5,300,127, 4,735,015, 4,634,587, 4,383,391, 4,372,080, 4,339,456,4,272,417 and 4,245,432, among others.

Useful seed coatings contain one or more binders in addition to thesubject microparticles.

Binders that are useful in the present invention preferably comprise anadhesive polymer that may be natural or synthetic and is withoutphytotoxic effect on the seed to be coated. The binder may be selectedfrom polyvinyl acetates; polyvinyl acetate copolymers; ethylene vinylacetate (EVA) copolymers; polyvinyl alcohols; polyvinyl alcoholcopolymers; celluloses, including ethylcelluloses, methylcelluloses,hydroxymethylcelluloses, hydroxypropylcelluloses andcarboxymethylcellulose; polyvinylpyrolidones; polysaccharides, includingstarch, modified starch, dextrins, maltodextrins, alginate andchitosans; fats; oils; proteins, including gelatin and zeins; gumarabics; shellacs; vinylidene chloride and vinylidene chloridecopolymers; calcium lignosulfonates; acrylic copolymers;polyvinylacrylates; polyethylene oxide; acrylamide polymers andcopolymers; polyhydroxyethyl acrylate, methylacrylamide monomers; andpolychloroprene.

The amount of binder in the coating can vary, but will be in the rangeof about 0.01 to about 25% of the weight of the seed, more preferablyfrom about 0.05 to about 15%, and even more preferably from about 0.1%to about 10%.

The agricultural actives that are useful in the subject microparticlesare those that are described above. The amount of active, and,therefore, the amount of microparticles, that is used for the treatmentof a seed will vary depending upon the type of seed and the type ofactive ingredients, but the treatment will comprise contacting the seedswith an amount of the microparticles that is pesticidally, or otherwise,effective. When insects are the target pest, that amount will be anamount of an insecticidal active that is insecticidally effective. Asused herein, an insecticidally effective amount means that amount ofinsecticide that will kill insect pests in the larvae or pupal state ofgrowth, or will consistently reduce or retard the amount of damageproduced by insect pests.

In general, the amount of agricultural active that is applied to theseed in the treatment will range from about 1 gm to about 2000 gm of theactive ingredient of the pesticide per 100 kg of the weight of the seed.Preferably, the amount of pesticide will be within the range of about 10gm to about 1000 gm active per 100 kg of seed, more preferably withinthe range of about 50 gm to about 800 gm active per 100 kg of seed, yetmore preferably within the range of about 100 gm to about 550 gm activeper 100 kg seed, and even more preferably within the range of about 200gm to about 500 gm of active per 100 kg of seed weight. Alternatively,it has been found to be preferred that the amount of the pesticide beover about 60 gm of the active ingredient of the pesticide per 100 kg ofthe seed, and more preferably over about 80 gm per 100 kg of seed.

The microparticles of the subject invention can be applied to the seedin the form of a coating. The use of a coating is particularly effectivein accommodating high pesticidal loads, as can be required to treattypically refractory pests, such as corn rootworm, while at the sametime preventing unacceptable phytotoxicity due to the increasedpesticidal load.

Optionally, a plasticizer can be used in the coating formulation.Plasticizers are typically used to make the film that is formed by thecoating layer more flexible, to improve adhesion and spreadability, andto improve the speed of processing. Improved film flexibility isimportant to minimize chipping, breakage or flaking during storage,handling or sowing processes. Many plasticizers may be used, however,useful plasticizers include polyethylene glycol, glycerol,butylbenzylphthalate, glycol benzoates and related compounds. The rangeof plasticizer in the coating layer will be in the range of from bout0.1 to about 20% by weight.

In addition to the coating layer, the seed may be treated with one ormore of the following ingredients: other pesticides including fungicidesand herbicides; herbicidal safeners; fertilizers and/or biocontrolagents. These ingredients may be added as a separate layer oralternatively may be added in the pesticidal coating layer.

The microparticle formulation may be applied to the seeds usingconventional coating techniques and machines, such as fluidized bedtechniques, the roller mill method, rotostatic seed treaters, and drumcoaters. Other methods, such as spouted beds may also be useful. Theseeds may be presized before coating. After coating, the seeds aretypically dried and then transferred to a sizing machine for sizing.Such procedures are known in the art.

The microparticle-treated seeds may also be enveloped with a filmovercoating to protect the coating. Such overcoatings are known in theart and may be applied using conventional fluidized bed and drum filmcoating techniques.

In yet another embodiment, a powdered form of the dry microparticles canbe mixed directly with seed. Optionally, a sticking agent can be used toadhere the powder to the seed surface. For example, a quantity of seedcan be mixed with a sticking agent and optionally agitated to encourageuniform coating of the seed with the sticking agent. The seed coatedwith the sticking agent can then be mixed with the dry microparticles.The mixture can be agitated, for example by tumbling, to encouragecontact of the sticking agent with the dry microparticles, therebycausing the microparticles to stick to the seed.

The treated seeds of the present invention can be used for thepropagation of plants in the same manner as conventional treated seed.The treated seeds can be stored, handled, sowed and tilled in the samemanner as any other pesticide treated seed. Appropriate safety measuresshould be taken to limit contact of the treated seed with humans, foodor feed materials, water and birds and wild or domestic animals.

Also included within the scope of this invention is a treated plant orits propagation material that includes a plant or its propagationmaterial that has been contacted with the formulation containing thepresent lignin-based matrix microparticles.

The following examples describe preferred embodiments of the invention.Other embodiments within the scope of the claims herein will be apparentto one skilled in the art from consideration of the specification orpractice of the invention as disclosed herein. It is intended that thespecification, together with the examples, be considered to be exemplaryonly, with the scope and spirit of the invention being indicated by theclaims which follow the examples. In the examples all percentages aregiven on a weight basis unless otherwise indicated.

EXAMPLE 1

This example shows the production of lignin-based matrix microparticlesfor the controlled release of imidacloprid.

An aqueous solution of methyl cellulose (1.09 g; Methocel A15LV,available from Dow Chemical Co.) was prepared in a 400 ml beaker bymixing with 89.71 g of water, and the solution was cooled to 4° C. in anice bath. An organic solution containing imidacloprid (1.7 g; availablecommercially in formulations under the trade names Admire®, Gaucho®,Confidor® and Winner®, all from Bayer AG), and lignin acetate (14.8 g;available from Aldrich) was prepared by mixing with methylenechloride(93.5 g, available from Aldrich) until all solids had gone intosolution. The organic solution was then added to the aqueous solution inthe beaker over a period of about 30 seconds, during which time themixture in the beaker was agitated with a high shear mixer (Silverson,Model L4R) equipped with a 6-hole screen. The mixture was agitated withthe high shear mixer for a total of 3 minutes at a setting of 3, duringwhich time a milky white emulsion was formed. The emulsion was thenremoved from the ice bath and stirred for 20 hours with a mechanicalstirrer while it was allowed to come to room temperature. During the 20hours, the methylenechloride evaporated from the mixture, leaving 94.33g of a white slurry of matrix microparticles. The microparticles had anaverage particle size of 7.3 microns as measured by a Coulter Counter.

Electron micrographs of the matrix microparticles were taken atincreasingly higher magnification and showed that the microparticleswere spherical particles having a distribution of sizes, but with few,or no, particles over about 20 microns in diameter. These microparticlesare shown in FIG. 1 at magnifications of 100× (FIG. 1(a)), 500× (FIG.1(b)), 1000× (FIG. 1(c)), and 2000× (FIG. 1(d)). Also noted in themicrographs was the almost total lack of free imidacloprid crystals inthe slurry. This was interpreted to mean that the majority of theimidacloprid was retained within the microparticles and not free insolution.

The relative amount of the active that is released into the environmentwithout control is termed the “readily extractable active” (REA). Asused herein, REA means the percent by weight of the total activeingredient that was added to the formulation that dissolved in water inthe following test:

REA was measured by adding the formulation to be tested to water in eachof two test tubes at room temperature, about 25° C. The total amount ofthe formulation added to one test tube was sufficient to provide anamount of the active ingredient that was about 80% of its solubilitylimit in water at that temperature. The total amount of the formulationadded to the other test tube was sufficient to provide an amount of theactive that was about 120% of the solubility limit. Both tubes were thenshaken vigorously for about 200 shakes. A sample of the mixture wasremoved from each tube and filtered through a 0.45 micron PTFE filter.The concentration of the active in the filtered liquid was measured ineach of the two test tubes and the percentage of the total amount ofactive that had been released into the water was calculated. The valueof the total amount of active that was released into the water wasdivided by the total amount of active that was initially added to thetube and the average of those values was multiplied by 100 and reportedas percent REA for the formulation. In the present formulation, theactive was imidacloprid, and the REA for the present microparticulateslurry was 8.3%. This reinforces the micrographs in indicating that mostof the imidacloprid in the formulation was initially present within themicroparticles and not free in the aqueous solution.

The rate of release of the imidacloprid was measured as a function oftime by the following method. A measured amount of a controlled releaseformulation was mixed with an amount of water at room temperature sothat the total concentration of active ingredient present in the aqueousmixture is no more than about ⅓ of the solubility limit of the active inwater at room temperature—about 25° C. The mixture was then mixed in abeaker with a magnetic stirrer. At intervals, aliquots of the mixturewere removed and filtered through a 0.45 micron PTFE filter. The amountof the active ingredient in the filtered solution was then measured. Forexample, when the active ingredient was imidacloprid, about 0.2 g/ltotal concentration of imidacloprid was added to the aqueous mixture andthe concentration of imidacloprid was measured by reverse phase HPLCwith UV detection.

The release rate of imidacloprid into an excess of water from themicroparticles described above was measured for over 6000 hours, and therelease rate is shown in FIG. 2. From the data, it appeared that thetime required for the exhaustion of one-half of the imidacloprid fromthe microparticles (the half-life, or t_(1/2)) was about 1000 hours,which was considered to be a release period of long duration for suchsmall particles.

After the slurry had been subjected to the release test for 42 days(about 1000 hours) a sample was taken and electron micrographs wereagain taken of the particles. As shown in FIG. 3, at successively highermagnifications of (a) 100×, (b) 500×, (c) 1000×, and (d) 2000×, it wasapparent that the microparticles were physically breaking down intocracked spheres or smaller fragments. It is not known whether release ofthe imidacloprid resulted in weakening the microparticles, or whetherwater-induced breakdown of the microparticles resulted in release of theimidacloprid. However, the phenomena appeared to occur concurrently.

EXAMPLE 2

This illustrates the formation of lignin-based matrix microparticleshaving a higher imidacloprid loading than in Example 1.

Lignin-based matrix microparticles for the controlled release ofimidacloprid were produced as described in Example 1, except that 10.9 gof lignin acetate was used, instead of 14.8 g, and 97.4 g ofmethylenechloride was used, rather than 93.5 g. After the removal ofmethylenechloride, 64.25 g of a white slurry of microparticles wascollected. The average particle size was 6.5 microns, and the REA was11.4%. No crystals of imidacloprid were apparent in an electronmicrograph of the slurry. The slurry was tested for release rate asdescribed in Example 1, and the release rate curve shown in FIG. 4indicated a t_(1/2) of about 2000 hours.

EXAMPLE 3

This illustrates the formation of lignin-based matrix microparticleshaving smaller size.

Lignin-based matrix microparticles for the controlled release ofimidacloprid were produced as described in Example 1, except that thesetting of the Silverson high shear device was operated at a setting of5.5, rather than 3. The average particle size was reduced to 5.6microns, and the REA was 7.2%. No crystals of imidacloprid were apparentin an electron micrograph of the slurry. The slurry was tested forrelease rate as described in Example 1, and the release rate curve shownin FIG. 5 indicated a t_(1/2) of about 2000 hours.

EXAMPLE 4

This illustrates the formation of lignin-based microparticles thatcontain silthiopham as the agricultural active.

Lignin-based matrix microparticles for the controlled release ofsilthiopham were produced as described in Example 1, except that thesetting of the Silverson high shear device was operated at a setting of5.5, rather than 3. The average particle size was 6.2 microns, and theREA was 1.1%. No crystals of silthiopham were apparent in an opticalmicrograph of the slurry.

The slurry was tested for release rate as described in Example 1 exceptthat the active is silthiopham instead of imidacloprid, and the releaserate curve is shown in FIG. 6.

COMPARATIVE EXAMPLE 1

This illustrates the formation of microparticles for the controlledrelease of imidacloprid from a poly(methyl methacrylate) matrix.

An aqueous solution of methyl cellulose (1.09 g; Methocel A15LV,available from Dow Chemical Co.) was prepared in a 400 ml beaker bymixing with 89.71 g of water, and the solution was cooled to 4° C. in anice bath. An organic solution containing imidacloprid (1.7 g; availablecommercially under the trade names Admire®, Gaucho®, Confidor® andWinner®, all from Bayer AG), and poly(methyl methacrylate), (PMMA),(14.80 g, having an average molecular weight of 120,000, and availablefrom Aldrich), was prepared by mixing with methylenechloride (93.5 g,available from Aldrich) until all solids had gone into solution. Theorganic solution was then added to the aqueous solution in the beakerover a period of about 30 seconds, during which time the mixture in thebeaker was agitated with a high shear mixer (Silverson, Model L4R)equipped with a 6-hole screen. The mixture was agitated with the highshear mixer for a total of 3 minutes at a setting of 3, during whichtime a milky white emulsion was formed. The emulsion was then removedfrom the ice bath and stirred for 20 hours with a mechanical stirrerwhile it was allowed to come to room temperature. During the 20 hours,the methylenechloride evaporated from the mixture, leaving 93.8 g of awhite slurry of matrix microparticles. Microscopic examination of theslurry showed that microspheres had been formed, but also showed thepresence of many crystals that were presumably free imidacloprid thathad not been incorporated into the microparticles.

It was concluded, therefore, that insufficient compatibility existedbetween the PMMA and imidacloprid to permit the successful formation ofmatrix microparticles for controlled release of imidacloprid.

All references cited in this specification, including without limitationall papers, publications, patents, patent applications, presentations,texts, reports, manuscripts, brochures, books, internet postings,journal articles, periodicals, and the like, are hereby incorporated byreference into this specification in their entireties. The discussion ofthe references herein is intended merely to summarize the assertionsmade by their authors and no admission is made that any referenceconstitutes prior art. Applicants reserve the right to challenge theaccuracy and pertinency of the cited references.

In view of the above, it will be seen that the several advantages of theinvention are achieved and other advantageous results obtained.

As various changes could be made in the above methods and compositionswithout departing from the scope of the invention, it is intended thatall matter contained in the above description and shown in theaccompanying drawings shall be interpreted as illustrative and not in alimiting sense.

What is claimed is:
 1. A formulation for the controlled release of anagricultural active, the formulation comprising predominantly sphericalmatrix microparticles having a matrix of a lignin derivative which issoluble in methylene chloride in an amount of at least 1% by weight at20° C. within which an agricultural active is distributed.
 2. Theformulation according to claim 1, wherein the microparticles have anaverage diameter of no larger than about 100 microns.
 3. The formulationaccording to claim 1, wherein the microparticles have an averagediameter of no larger than about 25 microns.
 4. The formulationaccording to claim 1, wherein the microparticles have an averagediameter of no larger than about 10 microns.
 5. The formulationaccording to claim 1, wherein the microparticles are capable ofreleasing the agricultural active into an infinite sink of water at roomtemperature for at least 1000 hours.
 6. The formulation according toclaim 1, wherein the lignin derivative is one that is soluble methylenechloride in an amount of at least about 10% by weight at 20° C.
 7. Theformulation according to claim 1, wherein the lignin derivativecomprises lignin acetate.
 8. The formulation according to claim 1,wherein the agricultural active is one that is soluble in water at 20°C. in an amount of less than about 2% by weight and is soluble inmethylene chloride in an amount of at least about 1% by weight.
 9. Theformulation according to claim 1, wherein the agricultural active is onethat is soluble in water at 20° C. in an amount of less than about 2% byweight and is soluble in methylene chloride in an amount of at leastabout 5% by weight.
 10. The formulation according to claim 1, whereinthe agricultural active comprises a material selected from the groupconsisting of pesticides, herbicides and growth regulators.
 11. Theformulation according to claim 1, wherein the agricultural activecomprises a compound that is selected from the group consisting ofacylalanines, alkanamides, amidines, anilides, anilinopyrimidines,aromatic hydrocarbons, chlorophenyls, arylaminopropionic acids,aryloxyalkanoic acids, aryloxyphenoxypropionates, auxins, avermectins,benzamides, benzenecarboxilic acids, benzilates, benzimidazoles,benzofurans, benzoic acids, benzonitriles, benzothiadiazinones,benzothiazolones, benzotriazines, benzoylureas, bipyridyliums,bis-carbamates, butyrolactones, carbamates, carbamoyltriazoles,chloroacetamides, chloronitriles, chloronicotinyls, cinnamic acids,coumarin anticoagulants, cyclodiene organochlorines, cyclohexanedioneoximes, cytokinins, diacylhydrazines, dicarboximides,2-dimethylaminopropane-1,3-dithiols, dimethyldithiocarbamates,dinitroanilines, dinitrophenols, diphenyl ethers, dithiocarbamates,DMI:imidazoles, DMI: pyridines, DMI:pyrimidines, DMI:triazoles,gibberellins, guanidines, halogenated alkanoic acids, hydroxyanilides,hydroxylbenzonitriles, imidazoles, imidazolinones, indandioneanticoagulants, isoxazoles, isoxazolidinones, juvenile hormone mimics,MBI:dehydrases, morpholines, alkylenebis(dithiocarbamates),chloronitriles, dimethyldithiocarbamates, guanidines, inorganics,phenylphridinamines, phosphonates, phthalimides, quinones, sulphamides,natural pyrethrins, neocorticoids, nitromethylene: neocorticoids,non-ester pyrethroids, N-phenyl carbamates, N-phenylphthalimides,organoarsenics, organochlorines, organophosphorous compounds,organotins, oxadiazines, oxadiazoles, oxathlins, oxozolidinediones,oxazolidinones, oxime carbamates, oxyacetamides, phanylamide:acylalanines, phenylamide: butyrolactones, phenylamide: oxazolidinones,phenylpyrazole herbicides, phenypyrazole insecticides,phenylpyridazines, phenylpyridinamines, phenylpyrroles, phenylureas,pheromones, phosphinic acids, phosphonates, phosphoroamidates,phosphorodithioates, phosphorothiolates, phthalamates, phthalimides,piperazines, polyoxins, pyrazoles, pyrazoliums, pyrethrins, pyrethroids,pyrethroid non-esters, pyridazinones, pyridazinone analogues, pyridines,pyridinecarboxamides, pyridinecarboxylic acids, pyrimidindiones,pyrimidines, pyrimidinols, pyrimidinyl carbinols, pyrimidinyloxybenzoiccompounds, pyrimidinyloxybenzoic analogues, quaternary ammoniumcompounds, quinolines, quinolinecarboxylic acids, quinones,semi-carbazones, strobilurin compounds,sulfonylaminocarbonyltriazolinones, sufonylureas, sulfamides, syntheticauxins, tetrazines, tetrazolinones, thiadiazoles, thiocarbamates,1,3,5-triazines, 1,2,4-triazinones, triazoles, triazolinones,triazolpyrimidines, triketones, uracils, ureas and mixtures thereof. 12.The formulation according to claim 1, wherein the agricultural active isa strobilurin compound that is selected from the group consisting ofmetominostrobin, picoxystrobin, famoxadone, azoxystrobin,kresoxim-methyl, trifloxystrobin and mixtures thereof.
 13. Theformulation according to claim 1, wherein the agricultural active is aherbicide that is selected from the group consisting of phenoxy aceticacids, 2,4-D, MCPA, phenoxy propionic acids, dichlorprop (2,4-DP),mecoprop (MCPP), phenoxy butyric acids, 2,4-DB, MCPB, benzoic acids,dicamba, picolinic acid compounds, picloram, triclopyr, clopyralid,quinclorac, naptalam, semicarbones, diflufenzopyr-sodium,chloro-s-triazines, atrazine, simazine, cyanazine, methoxy-s-triazines,prometon, methylthio-s-triazines, ametryn, prometryn, hexazinone,metribuzin, substituted ureas, diuron, fluometuron, linuron,tebuthiuron, uracils, bromacil, terbacil, benzothiadiazoles, bentazon,benzonitriles, bromoxymil, phenylcarbamates, desmedipham, phenmedipham,pyridazinones, pyrazon, phenypyriddazines, pyridate, propanil, amitrole,clomazone, fluridone, pyridazinones, norflurazon, isoxazoles,isoxaflutole, dinitroanilines, benefin, ethalfluralin, oryzalin,pendimethalin, prodiamine, trifluralin, pyridines, dthiopyr, thiazopyr,amides, pronamide, DCPA, carbamothioates (thiocarbamates), EPTC,cycloate, pebulate, triallate, butylate, molinate, thiobencarb,vernolate, seedling root inhibiting amides, napropamide, seedling rootinhibiting phenylureas, siduron, bensulfide, chloroacetamides,acetochlor, dimetenamid, propachlor, alachlor, metolachior, glyphosate,sulfosate, sulfonylureas, bensulfuron, chlorsulfuron, halosulfuron,nicosulfuron, prosulfuron, rimsulfuron, thifensulforon, tribenuron,chiorimuron, ethametsulfuron, metsulfuron, primisulfuron, oxasulfuron,triasulfuron, triflusulfuron, imidazolinones, imazamethabenz, imazamox,imazapic, imazapyr, imazaquin, imazethapyr, aryoxyphenoxyproprionates,diclofop-methyl, fenoxaprop-ethyl, fenoxaprop-p-ethyl,fluazifop-p-butyl, haloxyfop, quizalofop-p-ethyl, cyclohexanediones,clethodim, sethoxydim, tralkoxydim, nitriles, dichlobenil, benzamides,isoxaben, quinclorac, dilute sulfuric acid, monocarbamide dihydrogensulfate, herbicidal oils, bipyridyliums, diquat, paraquat,diphenylethers, aciflurofen, fomesafen, lactofen, oxyfluorfen,oxidiazoles, fluthiacet, oxadiazon, n-phenylheterocycles, carfentrazone,flumiclorac, sulfentrazone, glufosinate, organic arsenicals, DSMA, MSMA,asulam, endothall, ethofumesate, fosamine, difenzoquat, TCA, andmixtures thereof.
 14. The formulation according to claim 1, wherein theagricultural active is a fungicide that is selected from the groupconsisting of fludioxonil, fluquinconazole, silthiopham, difenoconazole,a mixture of fludioxonil and fluquinconazole or4,5-dimethyl-N-2-propenyl-2-(trimethylsilyl)-3-thiophencarboxamid, amixture of difenoconazole and fluquinconazole or4,5-dimethyl-N-2-propenyl-2-(trimethylsilyl)-3-thiophencarboxamid, and amixture of a thienol[2,3-d]pyrimidin-4-one and an azole fungicide, ananilinopyrimidine fungicide, a morpholine fungicide, a strubilurincompound, a pyrrole compound, a phenylamide, or a dithiocarbamatefungicide.
 15. The formulation according to claim 1, wherein theagricultural active comprises a compound that is selected from the groupconsisting of imidacloprid, acetamiprid, thiamethoxam, TI-435(clothiamidin), simeconazole, fluquinconazole, tebuconazole,silthiopham, terbufos, chlorpyrifos, fipronil, chlorethoxyfos,tefluthrin, fipronil, carbofuran, tebupirimfos, methoprene, hydroprene,and mixtures thereof.
 16. The formulation according to claim 1, whereinthe agricultural active comprises at least one compound that is selectedfrom the group consisting of imidacloprid, simeconazole, silthiopham,and mixtures thereof.
 17. The formulation according to claim 1, whereinthe agricultural active comprises imidacloprid and simeconazole.
 18. Theformulation according to claim 1, wherein the agricultural activecomprises simeconazole and silthiopham.
 19. The formulation according toclaim 1, wherein the agricultural active comprises imidacloprid andsilthiopham.
 20. A method of treating a plant or its propagationmaterial, the method comprising contacting the plant or its propagationmaterial with a formulation comprising predominantly spherical matrixmicroparticles having a matrix of a lignin derivative which is solublein methylene chloride in an amount of at least 1% by weight at 20° C.within which an agricultural active is distributed.
 21. The methodaccording to claim 20, wherein the plant or its propagation materialcomprises a seed of the plant.
 22. A treated plant or its propagationmaterial comprising a plant or its propagation material that has beencontacted with a formulation comprising predominantly spherical matrixmicroparticles having a matrix of a lignin derivative which is solublein methylene chloride in an amount of at least 1% by weight at 20° C.within which an agricultural active is distributed.
 23. The treatedplant or its propagation material according to claim 22, wherein theplant or its propagation material comprises a plant seed.